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De Novo Design of Photoactive Proteins

Applications are invited for a PhD fellowship/scholarship at Graduate School of Natural Sciences, Aarhus University, Denmark, within the Chemistry programme. The position is available from August 2024 or later.

Title:
De Novo Design of Photoactive Proteins

Research area and project description:
In this project, we will use recent advances in AI-based protein design for creating non-natural proteins with light-dependent functions. Nature has built fantastic light-activated proteins to control for example photosynthesis, plant physiology, and animal vision. Furthermore, in recent decades, photoactive proteins have found immense use as light-responsive tools for basic science and biotechnology incl. fluorescent proteins, optogenetic actuators, and photobiocatalysts. Almost all these tools have been engineered from natural proteins. Thus, our understanding of photoactive proteins largely relates to specific natural protein folds. However, there are many challenges of modern society that natural evolution has never been tasked to solve.                     

The aim of this project is to advance our abilities to create artificial photoactive proteins with folds and functions beyond those found in nature. Using chromophores as model cofactors, the project will explore, develop, and validate methods for reliably designing functional cofactor-binding proteins from scratch - also known as de novo protein design.

The central methods of the project include an equally important combination of computational protein design and experimental protein characterization.  Specifically, building on machine learning-based protein design algorithms (e.g. AlphaFold and RFdiffusion), we will develop protocols to stabilize chromophore binding pockets in de novo designed proteins. Experiments to validate and characterize the designs, will involve recombinant protein production, biophysical characterization, live cell fluorescence microscopy, advanced optical spectroscopy, and structure determination.

The expected outcome is a contribution of protein design principles and protocols, fundamental biophysical and photophysical insight, and new protein modules for synthetic/chemical biology tools such as biosensors for fluorescence microscopy.

To learn more, interested applicants are highly encouraged to read more on westberglab.com and contact Michael Westberg.

For technical reasons, you must upload a project description. When - as here - you apply for a specific project, please simply copy the project description above, and upload it as a PDF in the application. If you wish to, you can indicate an URL where further information can be found. 

Qualifications and specific competences:
Applicants should at least have finished one full year of a relevant Master’s program (60 ECTS) by July 2024.

The applicant should have an interdisciplinary drive and has preferably studied either: biophysical chemistry, biophysics, biochemistry, chemical biology, molecular biology, bioengineering, biotechnology, nanoscience or related fields.

The applicant is expected to have:

  • documented research experience at BSc and/or MSc level that includes wet lab work related to the above listed disciplines. 
  • at least basic programming skills within one major programming language (e.g., Python) and a desire to expand this skillset. If in doubt, contact Michael Westberg.
  • excellent English verbal and written skills

Experience with any of the following skills are a plus but not a requirement:

  • experimental skills: molecular cloning, recombinant protein expression, biophysical protein characterization, fluorescence microscopy, laser spectroscopy, mammalian cell culture, protein crystallography or cryo-EM.
  • computational skills: de novo protein design, molecular docking, molecular dynamics.

Place of employment and place of work:
The place of employment is Aarhus University, and the place of work is Department of Chemistry

Langelandsgade 140, 8000, Aarhus C, Denmark. 

Contacts:
Applicants seeking further information for this project are invited to contact: Assistant Professor Michael Westberg, westberg@chem.au.dk

How to apply:

For information about application requirements and mandatory attachments, please see the Application guide. Please read the Application guide thoroughly before applying.

When ready to apply, go to https://phd.nat.au.dk/for-applicants/apply-here/ (Note, the online application system opens 1 March 2024)

  1. Choose May 2024 Call with deadline 1 May 2024 at 23:59 CET.
  2. You will be directed to the call and must choose the programme “Chemistry”.
  3. In the boxed named “Study”: In the dropdown menu, please choose: “De Novo Design of Photoactive Proteins (DNDPhP)”

Please note:

  • The programme committee may request further information or invite the applicant to attend an interview.
  • The project will only be initiated if the graduate school/the faculty grants funding.

At the Faculty of Natural Science at Aarhus University, we strive to support our scientific staff in their career development. We focus on competency development and career clarification and want to make your opportunities transparent. On our website, you can find information on all types of scientific positions, as well as the entry criteria we use when assessing candidates. You can also read more about how we can assist you in your career planning and development.

Aarhus University’s ambition is to be an attractive and inspiring workplace for all and to foster a culture in which each individual has opportunities to thrive, achieve and develop. We view equality and diversity as assets, and we welcome all applicants. All interested candidates are encouraged to apply, regardless of their personal background.

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